The eye disease glaucoma is characterized by a permanent loss of visual function due to irreversible damage to the optic nerve. The several morphologically or functionally distinct types of glaucoma are typically characterized by an undesirable elevation of intraocular pressure (IOP), which is considered to be causally related to the pathological course of the disease. Continuously elevated IOP has been associated with the progressive deterioration of the retina and the loss of visual function. In some cases, ocular hypertension, a condition in which IOP is elevated, can present without apparent loss of visual function. However, patients with ocular hypertension are considered to be at a high risk for eventually developing the visual loss associated with glaucoma. Therefore, lowering IOP can be an objective for the treatment of glaucoma patients and for patients with ocular hypertension in order to decrease the potential for, or severity of, glaucomatous retinopathy. Unfortunately, many individuals do not respond well when treated with existing glaucoma therapies.
Glaucoma is currently diagnosed based on specific presenting indications such as optic nerve head changes and visual field loss. However, over half of the patient population with glaucoma are unaware of the disease state, and have already lost approximately 30-50% of retinal ganglion cells by the time of diagnosis. Thus, improved methods for early diagnosis of glaucoma are needed.
Patients known as normotension or low-tension glaucoma patients have relatively low IOP, yet present with glaucomatous visual field loss. These patients may benefit from agents that lower and control IOP, because glaucoma that is detected early and treated promptly may have reduced or reversible loss of visual function. Accordingly, screening techniques are needed that can identify patients at risk for glaucoma, or can detect glaucoma at an early stage before vision loss occurs.
Glaucoma pathology is often associated with changes to the trabecular meshwork. The trabecular meshwork (TM) is a structure associated with aqueous humor (AH) outflow from the eye. Decreases in AH outflow through the TM can cause increases in IOP and potentially result in glaucomatous visual field loss. Identifying potential causes of TM damage may prove to be advantageous for developing glaucoma therapies and/or screening methods.
Certain conventional therapeutic agents are directed at lowering IOP indirectly by, for example, inhibiting AH formation or increasing uveoscleral outflow, and do not address the pathogenic processes involved in glaucoma directly. Furthermore, many of these conventional agents have associated side effects which may render them undesirable as ocular therapeutic agents for lowering IOP or treating glaucoma.